castration Resistant prOstate caNcer
Conditions
Interventions
Trade Name: Xtandi Astellas Pharma Europe B.V.
Product Name: enzalutamide
Product Code: MDV3100
Pharmaceutical Form: Capsule
Product Name: docetaxel
Pharmaceutical Form: Concentrate and solvent for s
Sponsors
AZIENDA PROVINCIALE PER I SERVIZI SANITARI DELLA PROVINCIA AUTONOMA DI TRENTO
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients meeting all of the following criteria will be considered for enrollment into the study: 1. Histologically- or cytologically-confirmed prostate adenocarcinoma. 2. Metastatic disease. 3. Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following: a. Increase in measurable disease (RECIST 1.1) [15], and/or b. Appearance of new lesions, including those on bone scan (=2 new lesions on 2 consecutive bone scans if progression disease diagnosed on bone scan only) consistent with progressive prostate cancer, and/or c. Rising PSA defined as 2 sequential increases above a previous lowest reference value. Each value must be obtained at least 1 week apart. A PSA value of at least 2 ng/ml is required at study entry. d. Effective castration (serum testosterone levels =0.50 ng/dL) by orchiectomy and/or LHRH agonists or antagonist with or without anti-androgens. i. If the patient has been treated with LHRH agonists or antagonist (i.e., without orchiectomy), then this therapy should be continued. ii. If patients were either started on complete androgen blockade, or had a PSA response (defined by any reduction in PSA sustained for at least 3 months) after adding an antiandrogen, prior anti-androgen therapy should be stopped before randomization: at least 6 weeks for bicalutamide and nilutamide, and at least 4 weeks for flutamide, megestrol acetate and any other hormonal therapy. 4. More than 18 years. 5. Eastern Cooperative Oncology Group (ECOG) performance status =65 years) yes F.1.3.1 Number of subjects for this age range 232
Exclusion criteria
Exclusion criteria: Patients who have met all the above inclusion criteria listed in Section 4.2. will be screened for the following exclusion criteria: 1. Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. 2. Prior treatment with abiraterone acetate and/or enzalutamide 3. Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of randomization. Patients may be on biphosphonates prior to study entry. 4. Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow. 5. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease. 6. History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomization; 7. Inadequate organ and bone marrow function as evidenced by: a. Hemoglobin 1.5 x ULN; e. Total bilirubin >1.5 x ULN, f. Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated either according to Cockcroft-Gault formula. Creatinine clearance 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening. 10. Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event. 11. Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene; 12. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which chemotherapy has been completed >5 years ago and from which the patient has been disease-free for >5 years. 13. Participation in another clinical trial and any concurrent treatment with any investigational
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the candidate efficacy of docetaxel plus prednisone plus enzalutamide (Arm A) versus docetaxel plus prednisone(Arm B) in chemo-naïve mCRPC.;Secondary Objective: To compare the two study arms for: •activity, disease control and survival •symptom control and quality of life •toxicity profile ;Primary end point(s): PRIMARY ENDPOINT •rate of patients without progression (according to guideline of Prostate Cancer Clinical Trials Working Group 2 - PCWG2) at 6 months after docetaxel first administration •This end point may be preferred over PFS (using actual progression times) because phase II randomized trials are not usually blinded and there is a potential for bias in determining progression times because of a tendency for more frequent response assessments for case control patients. Using progression-free rate at a predetermined time from treatment initiation as the primary endpoint minimizes the chance for bias related to earlier outcome determinations for patients on the control arm.;Timepoint(s) of evaluation of this end point: 6 months after docetaxel first administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SECONDARY ENDPOINTS •Rate of objective response according to RECIST criteria •Rate of biochemical response according to PCWG2 •Kaplan-Meier estimates of progression-free survival •Kaplan-Meier estimates of overall survival •Kaplan-Meier estimates of biochemical progression-free survival •Rate of treatment-related mortality •Rate of toxicity-related protocol withdrawal •Scales of brief pain inventory (BPI) and analgesic score •Functional scales and items of Functional Assessment of Cancer Therapy-Prostate (FACT – P) questionnaire •Type and grade of any adverse reaction to treatment, according to Common toxicity criteria – adverse events (CTC-AE) v. 4.03 ;Timepoint(s) of evaluation of this end point: The study period will include the study treatment period (until 30 days after last docetaxel administration) and the follow-up period (until death or cut-off date, whichever comes first) | — |
Countries
Italy
Contacts
Public ContactMedical Oncology Department
AZIENDA PROVINCIALE PER I SERVIZI SANIT ARI TRENTO
Outcome results
None listed